Comparison of Purple Passion Juice (Passiflora edulis var. edulis) and Simvastatin on Lipid-lowering Effect of Hyperlipidemic Rats Model
Alfi Muntafiah1a, Tisna Sendy Pratama1b, Anisa Rachmawati1c, Dewi Wahyu Wulandari1d and Qodri Santosa2e 1 Department of Biochemistry, Faculty of Medicine, Jenderal Soedirman University, Purwokerto, Indonesia 2 Department of Child Health, Faculty of Medicine, Jenderal Soedirman University, Purwokerto, Indonesia
Keywords: Purple passion juice, lipid profile, hyperlipidemia, Simvastatin, propylthiouracil, total cholesterol
Abstract: Hyperlipidemia is a lipoprotein metabolic disorder characterized by high cholesterol and triglycerides in blood circulation. Non-pharmacological management efforts by consuming healthy foods are often the first choice. In the previous research, we found the antihypercholesterolemia potential of purple passion juice 4.2 mL/200gBB/day in experimental animals. This study aims to compare purple passion juice's effectiveness to Simvastatin in improving the lipid profile of the hyperlipidemic rats model. This true experimental study used 32 male Wistar rats, divided into 4 groups: K1 (normal control), K2 (hyperlipidemia control), K3 (purple passion juice 4.2 mL/200gBB/day), K4 (simvastatin 0.18 mg/200gBB/day). We used pork oil six mL/200gBB/day and Propylthiouracil (PTU) 12.5 mg/day, divided into two doses, for 14 days, by gavage, to induced hyperlipidemia. Blood sampling through retro-orbital veins was carried out at the end of induction (pre-test) and the end of the study (post-test) to measure the lipid profile. T-paired test on total cholesterol and triglyceride levels of the pre-post test showed a significant decrease in total cholesterol levels in K4 (p=0.00) and a significant decrease in triglyceride levels K3 (p=0.03), while in K1, there was a significant increase in both parameters. HDL levels decreased significantly in all groups. There was a significant difference in the one-way ANOVA test for both total cholesterol and triglyceride levels (p <0.05). Post Hoc test on post-test total cholesterol levels showed a significant difference in K2 v.s K4 (0.00), but there was no difference between K3 v.s K4 (p=0,54). The study concludes that Simvastatin was more effective in reducing total cholesterol levels; however, purple passion juice is more effective in lowering triglyceride levels.
1 INTRODUCTION initiate cellular damage, and play a role in atherosclerosis's pathophysiological process Cholesterol and triglycerides are the main lipid (Harikumar et al., 2013; Nghiem-rao, Mavis and components in the blood circulation (Harikumar et College, 2014). Management of hyperlipidemia al., 2013). Their normal blood circulation levels play requires a comprehensive strategy: pharmacological an essential role in normal physiological processes and non-pharmacological therapy. Pharmacological (Abumrad and Davidson, 2012). Increasing levels of therapy uses anti-lipid drugs, including Simvastatin, these lipid compounds in the circulation are known as a statin group, as the first-line drug. On the other hyperlipidemia (Harikumar et al., 2013). Lifestyle hand, non-pharmacological treatment is often the first changes and high calorie, saturated fat, and choice through a healthy lifestyle by consuming foods cholesterol-rich diet cause this condition (Arsana et and fruits high in antioxidants, phytosterols, low al., 2019). The increase in these compounds in the calorie, and rich fibre (Arsana et al., 2019). The circulation can lead to the formation of free radicals, indigenous systems of medicine have provided
a https://orcid.org/0000-0002-9791-1200 b https://orcid.org/0000-0003-1694-2054 c https://orcid.org/0000-0002-1126-4939 d https://orcid.org/0000-0002-8043-564X e https://orcid.org/0000-0002-1769-6652
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Muntafiah, A., Pratama, T., Rachmawati, A., Wulandari, D. and Santosa, Q. Comparison of Purple Passion Juice (Passiflora edulis var. edulis) and Simvastatin on Lipid-lowering Effect of Hyperlipidemic Rats Model. DOI: 10.5220/0010489301480154 In Proceedings of the 1st Jenderal Soedirman International Medical Conference in conjunction with the 5th Annual Scientific Meeting (Temilnas) Consortium of Biomedical Science Indonesia (JIMC 2020), pages 148-154 ISBN: 978-989-758-499-2 Copyright c 2021 by SCITEPRESS – Science and Technology Publications, Lda. All rights reserved
Comparison of Purple Passion Juice (Passiflora edulis var. edulis) and Simvastatin on Lipid-lowering Effect of Hyperlipidemic Rats Model
extensive plant data for the treatment of antihypercholesterolemia potential of purple passion hyperlipidemia. Various studies on local natural fruits juice (Muntafiah, Ernawati, et al., 2017). Through the and plants, among others, have proven their previous research, purple passion juice at a dose of effectiveness in treating it (Harikumar et al., 2013; 4.2 mL/200gBB/day significantly reduced blood Alam and Mishra, 2017). cholesterol levels in experimental animals Indonesia is a country rich in various tropical (Muntafiah, Ernawati, et al., 2017). Continuing the fruits, which are beneficial for health. Although previous research, still focusing on purple passion scientifically not confirmed about its efficacy, the juice, in this study, we wanted to report the practice of using this plant material is widely used as effectiveness of anti-hypercholesterolemia potential a preventive or first treatment (Barbalho et al., 2012; of purple passion juice compared to the standard drug, Maqbool et al., 2019). This is based on the general Simvastatin. belief that using these natural ingredients is free from side effects and is readily available in the surrounding environment (Kaur, Jasvir; Kaur, Satvinder; 2 MATERIALS AND METHODS Mahajan, 2013). According to the World Health Organization (WHO), about 80% of the world's 2.1 Subjects population, especially developing countries, use this plant to get it (Soares et al., 2012; Alam and Mishra, This true experimental study used 32 white male rats 2017). In line with the high public interest in the use (Rattus norvegicus) Wistar, 2-3 months old, and 125- of natural ingredients, the scientific community, 250 gr weight. The animals were obtained from the through their research and publication, has Laboratory of Pharmacology and Experimental demonstrated the beneficial health effects of Animals at Jenderal Soedirman University, consuming this plant due to its phytotherapeutic Purwokerto. The animals were kept in an properties (Matsui et al., 2010; Barbalho et al., 2012; environment with a temperature of 22 ± 2 ° C, 50% Soares et al., 2012). humidity, and a light-dark cycle for 12 hours Purple passion fruit (Passiflora edulis var. Edulis (Sambodo et al., 2019). They were acclimatized for Sims) is a tropical fruit that has been successfully seven days, placed in individual cages with the same developed in many countries in the world, including material, shape, and size, received AD II pellet and Indonesia. This native Brazilian plant, easy to aquadest ad libitum. They were divided into four (4) cultivate and grow in our environment but is often not groups: normal control (K1), hypercholesterolemia used because of its sour taste. In fact, behind the taste, control (K2), treatment with purple passion juice 4.2 this tropical fruit is rich in nutritional and mL/200gBB/day (K3), and treatment with phytochemicals components, making this exotic fruit Simvastatin 0.18 mg/200gBB/day (K4). has a beneficial health value. Based on research, purple passion fruit contains fibre, minerals, phenolic 2.2 Hypercholesterolemia Induction and ascorbic acids (Ramaiya et al., 2019). In Indonesia, research and publications regarding the Induction of hypercholesterolemia was carried out health benefits of this fruit are still limited. after the acclimatization period to the K2, K3, and K4 Previous research has studied the potential of groups. We used pork oil six mL/200gBB/day and various parts of the passion fruit plant as a herbal propylthiouracil (PTU) 12.5 mg/day dissolved in 1 medicine source. These studies included the effect of mL of water, divided into two doses, by gavage. the rind on the maintenance of glycemia (Barbalho et Induction was carried out for 14 days (Kusumastuty, al., 2012), mesocarp in reducing 2014; Muntafiah, Ernawati, et al., 2017). hypercholesterolemia (Corrêa et al., 2014; Ostrowski et al., 2015), fruit peel in cases of asthma (Ross et al., 2.3 Purple Passion Juice Preparation 2008), and also leaf extract as antidiabetic (Kanakasabapathi and Gopalakrishnan, 2015). Fresh purple passion juice is obtained from Pulisen, Exploring the potential of passion juice as an Boyolali, Central Java. Purple passion fruit is washed, antihypercholesterolemic agent has also been carried cut into two parts, and the pulp is taken, then squeezed out in previous studies (Damasceno et al., 2011; with a filter cloth to separate the juice from the seeds. Maricelma da Silva Soares de Souza, Sandra Maria Making purple passion juice is done every day to BArbalho, Debora Christina Damasceno, Marilza obtain fresh juice (Muntafiah, Pratama and Ati, Viera Cunha Rudge, Kleber Eduardo de Campos, 2019). 2012). In the previous study, we found the
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2.4 Blood Sampling post test of total cholesterol, triglyceride, and HDL levels in each group—the One Way Anova test was Blood samples were collected through the retro- conducted to compare the mean levels of parameters orbital vein using a hematocrit pipette. Before tested between groups. One Way ANOVA test was sampling, the animals have fasted for 10 hours. significant if it was obtained p <0.05 and continued During this time, the experimental animals were still with post Hoc LSD. given aqua dest ad libitum. Blood sampling was carried out twice, a pre-test (after induction of hypercholesterolemia) and post-test (end of research). 3 RESULTS Furthermore, the sample was inserted into a non- EDTA tube, centrifuged, and serum was taken. 3.1 Animal Weight
2.5 Variable Measurement Weight measurements were carried out five times during the research period. The first measurement Examination of lipid profile (total cholesterol, was carried out at the beginning of acclimatization, triglycerides, HDL) was carried out at Biochemistry whereas the second was carried out before the Laboratory, Faculty of Medicine UNSOED, induction. The third measurement was then filled Purwokerto. Total cholesterol levels were examined after hypercholesterolemia induction/before using the CHOD-PAP method, using the Dyasis kit. treatment followed by the fourth measurement, which Triglyceride levels were analysed using Glycerol-3 carried out in the first week of treatment. The final Phosphate-Oxidase (GPO) method, while HDL levels measurement was taken at the end of the research. were analysed using the CHOD-PAP method. The The average body weight of experimental animals sample was examined with a photometer 5010 during the research period is presented in Figure 1. (Robert Riele GmbH & Co KG, Germany) at a wavelength of 540 nm (Muntafiah, Ernawati, et al., 300 2017). 200 K1 100 K2 2.6 Data Analysis 0
weight (gr) K3 12345 Data analysis was carried out quantitatively. Data weighing time K4 distribution was tested with Shapiro Wilk, and Levene tested the homogeneity of the data. A paired t-test was conducted to compare the mean of the pre- Figure 1. Bodyweight of the Mice.
Table 1. Lipid profile of the animal model. Groups Lipid profile K1 K2 K3 K4 Total cholesterol (mg/dL) pre-test 67.5 ± 7.42a 125 ± 19.35b 104.67 ± 20.32b 133 ± 29.79b post-test 113.00 ± 21.79a 110.5 ± 16.82ab 84.17 ± 16.12b 79.67 ± 11.38 b delta* 45.5 -14.4 -20.50 -53.33 p pre-post ** 0.00 0.20 0.05 0.00 Triglycerides (mg/dL) pre-test 61.67 ± 18.81a 215 ± 88.95b 261 ± 96.17b 176.67 ± 102.83b post-test 186.83 ± 70.24a 161.17 ± 34.44a 139.67 ± 28.92 a 157.33 ± 45.89a delta* 125.16 -53.83 -121.33 -19,34 p pre-post ** 0,02 0,25 0,03 0,6 HDL (mg/dL) pre-test 85.33 ± 41.10a 109.33 ± 24.41a 79.67 ± 23.13a 82.17 ± 14.46a post-test 46.17 ± 8.57a 51.33 ± 13.49a 48.67 ± 9.22 a 37.5 ± 9.29 a delta* -39.16 -58 -31 -44.67 p pre-post ** 0,054 0,00 0,03 0,00 * Delta (the mean difference between pre-test and post-test, positive indicates an increase, negative indicates a decrease. ** p<0,05 in each column shows a significant difference between pre-test and post-test. a,b Different notations on the same line indicate significant differences.
150 Comparison of Purple Passion Juice (Passiflora edulis var. edulis) and Simvastatin on Lipid-lowering Effect of Hyperlipidemic Rats Model
3.2 Lipid Profile experimental animals rats aged 8-16 weeks is 37-85 mg/dL and triglycerides 20-114 mg/dL (Giknis and Based on Table 1. we can see that the normal control Clifford, 2008). The results of examining total group (K1) had a mean total cholesterol level of 67.5 cholesterol levels in the normal group were not much mg/dL, triglycerides 61.67 mg/dL, and HDL 85.33 different from previous studies (Muntafiah, Yulianti, mg/dL. Hyperlipidemia induction using pork oil and et al., 2017; Muntafiah, Ernawati, et al., 2017). propylthiouracil in the K2, K3, and K4 groups, Meanwhile, in the induced group (K2, K3, K4), total significantly increased the total cholesterol and cholesterol levels were >110 mg/dL, and triglycerides triglyceride levels. T-paired test on pre-post test total were >170 mg/dL. The hyperlipidemia induction cholesterol levels showed a significant decrease in K4 technique can increase total cholesterol and groups. On the other hand, in the normal control triglyceride levels higher than the previous study. It group, there was a considerable increase. Likewise, was three mL/200gBB/day of pork oil and two for triglyceride levels, the paired t-test showed a mL/200gBB/day duck egg yolk for ten days significant decrease in triglyceride levels only in K3, (Muntafiah, Ernawati, et al., 2017. Another one was while in K1, there was a considerable increase. giving pure cholesterol of 0.03 grams and 1 gram of Meanwhile, HDL levels decreased significantly in all pork oil for 28 days (Sambodo et al., 2019). All the groups. One Way ANOVA test was carried out on administration has not propylthiouracil 12.5 mg/day, pre-test total cholesterol and triglyceride levels (after and a high-fat feed mixture of quail egg yolk and hypercholesterolemia induction) showed a significant ducks egg yolk for 21 days (Untari and Pramukantoro, difference in the mean levels of total cholesterol and 2020). Pork oil contains about 38-43% saturated fatty triglycerides (p <0.05). Furthermore, the post hoc test acids and cholesterol. Pork oil continuously for 14 results showed a significant difference between K1 days resulted in increased cholesterol and triglyceride and K2, K3 and K4 (this indicates the success of levels, accompanied by increased lipoproteins hypercholesterolemia induction). Furthermore, one (hyperlipoproteinemia) in the blood. (Kusumastuty, Way ANOVA test for total cholesterol and 2014). Meanwhile, PTU can inhibit thyroid cells in triglyceride levels showed a significant difference (p experimental animals to inhibit thyroid hormone <0.05). Post Hoc test on cholesterol levels showed a production and results in hyperthyroidism (Kurniati significant difference (p <0.05) in K2 v.s K4. et al., 2018). This condition directly affects However, there was no difference between K3 v.s K4 lipoprotein metabolism, increasing cholesterol levels (p = 0.54). (Untari and Pramukantoro, 2020). Propylthiouracil (PTU) is a thyroid hormone antagonist. Under normal circumstances, the thyroid hormone can increase fat 4 DISCUSSION metabolism. PTU is an antithyroid substance that can inhibit the formation of thyroid hormones that play a role in lipolysis so that inhibition of this thyroid A high-fat diet is directly linked to hyperlipidemia in increases blood cholesterol concentrations by humans. To test the herbal effect on reducing expanding endogenous cholesterol biosynthesis circulating lipids, an experimental study was carried (Diah et al., 2012; Kurniati et al., 2018). out with an experimental animal model of Based on this study, at the end of the research hyperlipidemia in the laboratory (Leite Matos et al., period, a significant increase in total cholesterol and 2005). Animal models used to identify herbal triglyceride levels occurred in K1 as a standard remedies' effectiveness can mimic human control. Various factors, including dietary factors, can pathophysiology (Briggs et al., 2014). In this study, cause this. In this study, experimental animal feed we made an experimental animal model of with AD II pellets, the fat content in it at least 4%, is hyperlipidemia. Hyperlipidemia induction was done thought to be one factor that causes an increase in by giving pork oil six mL/200gBB/day (Kusumastuty, total cholesterol and triglyceride levels. Meanwhile, 2014) and propylthiouracil (PTU) 12.5 mg/day for 14 in the K3 group, giving purple passion juice 4.2 days (Untari and Pramukantoro, 2020) by gavage. mL/200gBB/day for 14 days can reduced total This induction technique can increase total cholesterol and triglyceride levels (Table 1). Previous cholesterol and triglyceride levels in Wistar rats. research by Soares et al. showed the same thing where Based on this research, in the regular control group, P.edulis 1,000 mg/kg given twice a day for 28 days the mean total cholesterol was 67.5 mg/dL, and the showed the effect of improving lipid profile by average triglyceride level was 61.67 mg/dL. increasing HDL levels, lowering total cholesterol According to the reference, this average level states levels, and improving lipid peroxidation in Wistar's that the range of normal total cholesterol levels for
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Rat (Soares et al., 2012). Something different, in our cholesterol levels by inhibiting cholesterol study, purple passion juice can reduce triglyceride reabsorption from bile salts in the intestine. This fibre levels significantly. will undergo fermentation in the intestine and then What components are contained in purple passion turn into short-chain fatty acids. It can increase the juice so that they can reduce total cholesterol and intestinal contents' viscosity so that the bile salts' triglyceride levels? Medical plant research generally cholesterol is excreted in the faeces (Matsui et al., carries out on unrefined plant extract materials that 2010). have various elements. It is said that the bioactive compounds contained therein can work together synergistically to produce an effect (Moreira et al., 5 CONCLUSION 2014; Briggs et al., 2014). Likewise, purple passion juice's antihyperlipidemic potency can be caused by The provision of purple passion juice 4.2 various bioactive compounds contained in it. The mL/200gBB/day can improve the lipid profile of essential nutrients needed by the body are found in hyperlipidemia animals model by reducing total this juice. This fruit juice contains much fibre, 2.81% cholesterol and triglyceride levels. Simvastatin is protein, 6.57% carbohydrates, and <0.5% fat content. more effective in lowering total cholesterol levels; In 247 mL (1 cup) of juice contains 24% K, 60-80% however, purple passion juice is more effective in Mg,> 80% P, and 90% Fe of the recommended lowering triglyceride levels. The administration of dietary allowance of minerals. It has 1137 mg / 100 g purple passion juice and Simvastatin 0.18 of citric acid (Ramaiya et al., 2019). In addition to mg/200gBB/day both had the same effectiveness in nutritional components, various literature through reducing total cholesterol levels in experimental their research state that purple passion fruit contains animals. multiple phytochemical compounds such as polyphenols, carotenoids, and vitamins (Matsui et al., 2010) insoluble fibre fraction which is beneficial for health. Purple passion fruit contains 1,060% ACKNOWLEDGMENTS flavonoids, 1.160% carotenoids, and 0.012% alkaloids. Flavonoids can lower total cholesterol This research was funded by the Institute for levels in the blood (Matsui et al., 2010) (Kusumastuty, Research and Community Service (LPPM), Jenderal 2014) through the same mechanism as Simvastatin, a Soedirman University, Purwokerto, Indonesia, standardized and first-line drug in lowering through BLU grant (Competency Improvement cholesterol levels, by inhibiting the action of the Scheme). enzyme 3-hydroxy 3-methyl glutaric coenzyme A reductase (HMG Co-A reductase) on cholesterol synthesis in the liver (McFarland et al., 2014). REFERENCES Besides, flavonoids can also reduce cholesterol absorption and increase cholesterol conversion into Abumrad N. A. and Davidson N.O. (2012) 'Role of the gut bile acids so that cholesterol levels in the blood in lipid homeostasis', Physiol Rev, 92(3), pp. 1061– decrease (Yunarto et al., 2019). Beta carotene can 1085. DOI: 10.1152/physrev.00019.2011. reduce cholesterol absorption in the intestines and Alam G. and Mishra A.K. (2017) 'Traditional and Modern increase the excretion of cholesterol through faeces. Approaches for Standardization of Herbal Drugs: A This situation causes the liver to make cholesterol in Review', Acta Biomed Scientia, 4(1), pp. 40–55. DOI: the blood converted into bile acids to reduce blood 10.21276/abs.2017.4.1.9. Arsana P.M., Rosandi M., Manaf A., Budhiarta A.A.G., cholesterol (Silva et al., 2013). The content of vitamin Permana H., Sucipta K.W., Lindarto D., Adi S., C and fibre in purple passion fruit is also thought to Pramono B., Harbuwono D.S., Shahab A., Sugianto, play an active role in lowering blood cholesterol Karimi J., Purnomo LB., Yuwono A., Suhartono T. levels. Vitamin C works by influencing lipoprotein (2019) . Pedoman Pengelolaan Dislipidemi di lipase activity and carnitine synthesis. Lipoprotein Indonesia 2019, Pb. Perkeni, p. 9. doi: lipase (LPL) is an enzyme that plays a role in 10.1002/bit.22430. separating triglycerides from chylomicrons and Barbalho S.M., de Souza M.S.S., Silva J.C.P, Mendes C.G., VLDL. LPL catalyzes the breakdown of triglycerides de Oliveira G.A, Costa T. and Farinazzi-Machado into unesterified fatty acids and brings them to the F.M.V. (2012) 'Yellow passion fruit rind ( Passiflora edulis ): an industrial waste or an adjuvant in the adipose tissue for reprocessing and storage as maintenance of glycemia and prevention of triglycerides. Fibre content can reduce total
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